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Sequencing Therapy, Managing Toxicities, and Addressing Resistance in Atypical EGFR-Mutated NSCLC

Slideset

Review these downloadable slides on treatment sequencing, mechanisms of acquired resistance, and adverse event management in patients with atypical EGFR-mutated NSCLC. Current guideline recommendations and clinical trial evidence supporting subsequent-line treatment strategies for patients with uncommon EGFR mutations or EGFR exon 20 insertions are highlighted. Key findings from the CHRYSALIS-2, MARIPOSA-2, TROPION-Lung01/05, WU-KONG1B, and REZILIENT1 trials provide efficacy and safety data for amivantamab-based regimens, datopotamab deruxtecan, sunvozertinib, and zipalertinib. The slides also address the role of repeat molecular testing in identifying resistance mechanisms, considerations for managing CNS metastases, and strategies to prevent and manage treatment-related toxicities, including dermatologic adverse events, infusion-related reactions, venous thromboembolism, and stomatitis, to support individualized treatment decisions and continuity of care. 

Released: November 13, 2026

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Faculty

Alexander Spira

Alexander Spira, MD, PhD, FACP

CEO
Next Oncology
Fairfax, Virginia

Provided by

Provided by Clinical Care Options, LLC dba Decera Clinical Education

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Supporters

This activity is supported by an educational grant from Johnson & Johnson.

Johnson & Johnson

Target Audience

This activity is intended for oncologists, physician assistants, nurse practitioners, nurses, pharmacists, and other healthcare professionals who care for patients with EGFR-mutant NSCLC.

Learning Objectives

Upon completion of this activity, participants should be able to:

  • Apply current guideline recommendations and emerging clinical evidence to optimize comprehensive biomarker testing and the identification of atypical EGFR alterations in patients with NSCLC

  • Individualize treatment selection and sequencing for patients with atypical EGFR-mutant NSCLC by integrating molecular subtype, patient-specific factors, and the latest efficacy and safety data

  • Incorporate molecular reassessment and an understanding of resistance mechanisms into evidence-based treatment decisions following disease progression

  • Implement multidisciplinary strategies to proactively monitor and manage treatment-related adverse events, optimize adherence, and support patient-centered care across the treatment continuum